γδ T cell-stromal networks modulate matrix composition and vascularity in foreign body response.

Abstract

Immune-stromal crosstalk governs tissue fibrosis, which is marked by dysregulated extracellular matrix (ECM) production and aberrant vasculature. Here, we investigate how γδ T cell interactions with stromal cells shape fibrosis in the foreign body response in a murine biomaterial implant model. During the acute reaction, type-1 (γδIFNγ) and type-17 (γδ17) γδ T cell subsets accumulate at the implant site. While γδIFNγ cells decrease as fibrosis progresses, activated γδ17 cells persist as dominant interleukin-17 producers. The γδ17 cell compartment expands with aging and high-fat diet, both factors associated with chronic inflammation and fibrosis. Fibroblasts co-cultured with γδ17 cells exhibit increased expression of collagen genes and intercellular communication inference links γδ T cell ligands to activation of ECM remodeling and vascular development programs in fibroblasts and endothelial cells. Finally, genetic deletion of γδ T cells in mice alters expression of ECM components and increases vessel size within the fibrotic matrix. Altogether, our findings implicate γδ T cells in regulating stromal cell behavior to modulate composition and vascularity of fibrotic tissues.